Transcriptome analysis of five-toed jerboa organs reveals high-altitude adaptation mechanisms.

High-altitude environments are characterised by extreme conditions, including hypoxia, low temperatures, and intense ultraviolet radiation. Mammals inhabiting these environments have evolved unique adaptive mechanisms, the study of which elucidates survival strategies and evolutionary pathways under extreme conditions. Understanding how native high-altitude animals respond to such environments is highly important. This study investigated the high-altitude adaptation mechanisms of the five-toed jerboa (Orientallactaga sibirica) distributed in Qinghai Province (4229 m) and Hebei Province (498 m), China, through comparative transcriptomic analysis of heart, lung, and kidney tissues. The results revealed greater mRNA transcriptional differences in the lung tissue than in the heart and kidney tissues of high-altitude jerboas, indicating heightened lung sensitivity to high-altitude conditions. In lung tissue, high-altitude jerboas show differential expression of genes related to the Complement and Coagulation cascades, Heme binding, Oxidation-reduction process (such as MASP1, A2M, SERPING1, CD55, FGA, C5AR1, and KNG1), which may be associated with modulating immune functions to mitigate hypobaric hypoxia, intense radiation, and cold-induced damage and reducing thrombosis and inflammation risks. Heart tissue exhibits differential expression of Oxidative phosphorylation and Lipid metabolism genes (such as NDUFC2, NDUFA3, NDUFS4, COX4I2, PAFAH1B3, SGMS2 and PPAR2B), which may help maintain energy equilibrium under hypoxic and cold challenges. Kidney tissue exhibits differential enrichment of pathways such as arachidonic acid metabolism and steroid hormone biosynthesis mediated by genes including CYP4A11, CYP2C29, GPX2, PTGDS, CBR1, and UGT2B31, which may help coordinate vascular regulation, immune response, and oxidative balance to maintain systemic homeostasis. These pathways and genes are differentially enriched and expressed between high-altitude and low-altitude five-toed jerboas, which may be candidates for further functional studies of plateau environmental adaptability. Our findings provide candidate genes and pathways for intraspecies adaptations across microenvironments and highlight the need for further functional validation.