Integrated Transcriptomic and Metabolomic Analysis Reveals Myocardial Adaptation Mechanisms in Plateau Pikas...

The Qinghai-Tibet Plateau, with an elevation of 4000 m above sea level, is rich in biological resources, and all the native creatures are exposed to extremely inhospitable environmental challenges. However, the detailed adaptation mechanisms of the native organisms to such an environment are still unclear. In this study, in-depth high-throughput RNA-Seq sequencing and metabolome data were deployed to depict the transcription and metabolism landscape of pikas living at 4630 and 2600 m altitude to elucidate the multilayer adaptation mechanisms of pikas to the environment of the Qinghai-Tibet Plateau. We identified significant variations in transcription and metabolism between pikas from 4630 and 2600 m. Various genes functioned in inflammatory-related pathways, including inflammatory mediator regulation of TRP channels and GnRH/HIF-1/p53/TNF signaling pathways, which were more active in pikas from 4630 m. Immune-response-related genes were overall downregulated in high-altitude pikas (e.g., genes for pro-inflammatory mediator synthesis and immune cell recruitment); this may represent a potential adaptive immunomodulatory mode in response to hypoxic stress. The expression of genes involved in cardiac muscle contraction and oxidative phosphorylation pathways was lower in pikas from 4630 m, leading to advantages for pikas in obtaining sufficient oxygen. Pikas from 4630 m have a more active metabolism relevant to amino acids and lipids, which provides energy for pikas to adapt to a high-altitude environment. Metabolome results reach a consensus with metabolic analysis from the transcriptome that pikas from 4630 m contain high levels of various amino acids and lipids. Overall, our study reveals multi-layer adaptive signatures in the left ventricle of plateau pikas at both transcriptional and metabolic levels, advancing our understanding of how Ochotona curzoniae adapts to high-altitude hypoxia on the Qinghai-Xizang Plateau.