Respiratory system

The respiratory system includes the upper and lower airways and lungs, supporting airflow, gas exchange and protection against inhaled particles and pathogens. The conducting airways transport, warm, humidify and filter inhaled air, while the lungs contain specialized alveolar structures responsible for oxygen and carbon dioxide exchange. The respiratory system also contains specialized sensory and immune cells involved in detecting environmental stimuli and responding to inhaled substances.

The sampled respiratory tissues include olfactory epithelium, nasopharynx, larynx, trachea, bronchus and lung in all four species, enabling comparisons across different regions of the respiratory tract. However, human RNA expression data are available only for the lung, limiting direct cross-species transcriptomic comparisons to this tissue. Additional human protein expression data for the bronchus and nasopharynx are available in the HPA Tissue Resource, providing complementary information about protein localization and expression in these regions.

Figure 1. Tissue sample overview and the hierarchy of grouped tissues representing the respiratory system

The mammalian tissue represention of the respiratory system is separated into olfactory epithelium, upper respiratory system and lung.

HPA011316 nasopharynx HPA004331 bronchus HPA042638 lung

Comparative transcriptomics of the mammalian respiratory system

The transcriptomic data is used to identify genes with elevated expression in individual tissues or groups of tissues, classified into three categories:

Tissue enriched: Genes with elevated expression in a single tissue compared with all other tissues.
Group enriched: Genes with elevated expression in a limited group of tissues compared with the remaining tissues.
Tissue enhanced: Genes with elevated expression in one or more tissues compared with the average expression across tissues (gap ratio ≥2)

Tissue specificity is evaluated at two levels: first, within each species using all available tissue types, and second, using only tissues that can be directly compared between the species and human. This distinction makes it possible to explore both tissue-specific expression within each species and the conservation of expression patterns across evolution.

The results can be explored for individual genes on the gene summary pages or searched to identify genes with specific expression patterns. To assess evolutionary conservation, pairwise overlap analysis compares each species individually with human, identifying genes that share the same tissue specificity classification in corresponding tissues and quantifying the extent of overlap between species.

Tissue	Species	Elevated	Human elevated overlap
Tissue	Species	Elevated	Complete overlap	Partial overlap
Lung	Macaque	176	13	22
	Mouse	227	13	23
	Rat	203	13	21
	Pig	89	9	10
Olfactory epithelium	Macaque	71	n/a	n/a
	Mouse	441	n/a	n/a
	Rat	327	n/a	n/a
	Pig	81	n/a	n/a
Upper respiratory system	Macaque	438	n/a	n/a
	Mouse	253	n/a	n/a
	Rat	196	n/a	n/a
	Pig	163	n/a	n/a

Olfactory epithelium

The olfactory epithelium contains sensory neurons responsible for detecting odorants, together with supporting and basal cells. Rodents have a proportionally extensive olfactory epithelium and large repertoires of functional olfactory receptor genes, whereas primates rely relatively more on vision, making olfactory tissues particularly interesting for evolutionary comparisons.

Species coverage

Upper respiratory system

Nasopharynx

The nasopharynx forms part of the upper respiratory tract and contains respiratory epithelium, mucus-producing cells and associated immune tissues. Its epithelial organization and the distribution of mucosa-associated lymphoid tissue differ between species, particularly between rodents and larger mammals, potentially influencing immune and secretory gene expression.

Larynx

The larynx protects the lower airways during swallowing and contributes to vocalization through specialized muscles and vocal fold tissues. Its cartilage, epithelial organization and vocal fold structure differ between species, reflecting variation in vocal communication and airway anatomy.

Trachea

The trachea contains a ciliated respiratory epithelium that transports mucus and trapped particles towards the pharynx. Submucosal gland distribution, epithelial cell composition and cartilage organization vary across mammals, with humans and larger mammals generally having more extensive airway gland systems than mice and rats.

Species coverage

Lung

The lungs contain alveoli specialized for gas exchange, together with airways, blood vessels and immune cells. Lung architecture differs across mammals in the organization of lobules, connective tissue septa and distal airways; pigs also have a prominent population of pulmonary intravascular macrophages that is not normally present to the same extent in healthy humans and laboratory rodents. This difference is particularly relevant for comparing immune-related gene expression.

Bronchus

The bronchi are lined by a specialized epithelium containing ciliated, secretory and basal cells, with supporting cartilage and smooth muscle. The relative abundance and distribution of epithelial cell types differs between species, particularly between primates and rodents, where secretory club cells become prominent in smaller airways.

Species coverage

Sampling and tissue classification

Lung samples were collected from the peripheral regions of the lung, enriched for alveolar tissue, whereas bronchus samples were collected from larger, cartilage-supported airways. Although these samples represent different anatomical compartments, they share many molecular characteristics and are therefore grouped into a single main tissue type, lung, for the tissue specificity analysis. The individual samples remain available for exploring regional differences in gene expression.