Rising floor and dropping ceiling: organ heterogeneity in response to cold acclimation of the largest extant amphibian.

Low temperature imposes strong selective pressure on ectotherms. To maximize their overall fitness under cold conditions, the ectotherms may either try to maintain their physiological activities through metabolic compensation or enter into metabolic depression; however, some species adopt both strategies to cope with different degrees of cold. Nevertheless, how these two seemingly opposite strategies are coordinated has rarely been elucidated. Here, we investigated the molecular strategy underlying the cold acclimation of , the largest extant amphibian, using multi-organ metabolomics and transcriptomics. The results showed remarkable organ heterogeneity in response to cold. While most organs showed transcriptional upregulation of metabolic processes, the heart exhibited downregulation. This heterogeneity explained the adaptive reorganization in resource allocation, which compensates for metabolic maintenance by compromising growth. Importantly, the cardiac function might constitute a 'ceiling' to constrain the space for compensation, especially under colder conditions. Additionally, the opposite transcriptional regulation of oxidative phosphorylation and other pathways might also shape the overall metabolic capacity under cold conditions. The heterogeneity in cold responses may have directed a shift in cold adaptive strategy from compensation to depression with a drop in temperature. These results provide a novel insight into the regulatory mechanisms underlying cold survival strategies of ectotherms.