Hypoxic response patterns in lung tissue: An integrated analysis of comparative physiological and transcriptomic studies from Neodon fuscus and Lasiopodomys brandtii

Oxygen (O2) is essential for the survival and reproduction of most species. However, in recent years, with global climate change and the increasing impact of human activities on the ecosystem, the frequency of extreme environmental events, such as heat waves, cold waves, droughts, and floods, has increased, resulting in dramatic changes in environmental oxygen concentration (hypoxic environment, etc.), threatening the survival of animals and pushing them toward extreme adaptation. In this context, how organisms, especially those with differences in original habitats, adapt to low oxygen environment is particularly important. In this study, we systematically analyzed hypoxic response patterns in lung tissues of small rodents Neodon fuscus, Lasiopodomys brandtii, and Mus musculus with different experiences of natural hypoxia tolerance through laboratory simulation of hypoxia environment, combined with hematological, histological, and transcriptomic analysis. Our results show that all three species exhibit increased antioxidant defense and damage repair ability to a certain extent under hypoxia, although the specific molecular mechanisms are not the same. L. brandtii showed better damage repair ability than the others, which is likely to be closely related to the intermittent hypoxia environment experienced in the natural environment, and genes such as Glrx5, Prdx2, Col1a1, Lama1, and Eln may play a crucial role in this process. In addition, we found that both N. fuscus and L. brandtii appropriately enhanced oxygen transport in tissues under hypoxic conditions, with a series of functional genes related to hemoglobin synthesis and vascular smooth muscle contraction were significantly up-regulated in both species of voles, such as Actg2, Ptgir, Alas2, Hba, Hbb and Bpgm. Our results, to a certain extent, reveal the differences and similarities of hypoxic response patterns in lung tissues of small rodents with different hypoxic life histories and provide a relatively perfect analytical paradigm for related studies.