Abstract: High-altitude and marine mammals inhabit distinct ecosystems but share a common challenge: hypoxia. In response to low-oxygen environments, they have developed similar phenotypic adaptations in their lungs, notably a high density of elastic fibers. In this study, we explore how high-altitude and marine mammals adapt to pulmonary fibrosis and hypoxic environments through molecular mechanisms, using comparative genomics and convergent evolution analysis from multiple perspectives. We observed significant expansion or contraction in certain gene families, convergently in both high-altitude and marine mammals, closely associated with processes such as pulmonary fibrosis. Particularly, KRT17 and KRT14 in the keratin gene family may relate to the phenotype of these hypoxia-tolerant mammals having abundant elastic fibers in their lungs. Through selection pressure analysis and amino acid substitution analysis, we identified multiple genes undergoing convergent accelerated evolution, positive selection, and amino acid substitution in these species, associated with adaptation to hypoxic environments. Specifically, the convergent evolution of ZFP36L1, FN1, and NEDD9 genes contributes to the extensive elastic fibers in the lungs of high-altitude and marine animals, facilitating adaptation to hypoxia. Additionally, we noted convergent amino acid substitutions and gene loss in genes related to sperm development, differentiation, and spermatogenesis. For instance, amino acid substitutions in the SLC26A3 gene and pseudogenization of CFAP47, which was confirmed by PCR, were identified in high-altitude and marine mammals. These genetic alterations may be linked to changes in the reproductive capabilities of these animals. Overall, our study offers novel perspectives on the adaptation of high-altitude and marine mammals to hypoxic environments, particularly focusing on pulmonary fibrosis.