Respiratory Adaptations to High‐Altitude Hypoxia in Deer Mice ( Peromyscus maniculatus )

The unremitting hypoxia at high altitudes challenges small endotherms to extract enough oxygen from the environment to survive, exercise, and generate enough heat for thermoregulation. We compared the control of breathing and pulmonary gas‐exchange between highland and lowland populations of deer mice to determine the physiological specializations important for living in high‐altitude hypoxia. Mice were acclimated to normoxia or hypobaric hypoxia (simulating hypoxia at ~4300 m elevation) for 4–5 months. The hypoxic ventilatory response (HVR) was measured using whole‐body and restraint plethysmography in response to step‐wise decreases in inspired O 2 fraction. Hypoxia acclimation enhanced the HVR in lowlanders, such that total ventilation and arterial saturation were higher across a range of inspired O 2 . Hypoxia acclimation also made breathing pattern more effective in lowlanders, as reflected by higher tidal volumes and lower breathing frequencies at a given total ventilation, and it allowed lowlanders to maintain higher heart rates in deep hypoxia. In contrast, hypoxia acclimation had no effect on these traits in highlanders, who exhibited a fixed HVR and breathing pattern that was similar to hypoxia‐acclimated lowlanders, and highlanders also maintained higher arterial saturations in hypoxia than lowlanders. In contrast, hypoxia acclimation similarly enhanced the hypercapnic ventilatory response (measured in normoxia during step‐wise increases in inspired CO 2 , from 0% to 6%) in both populations. Therefore, ventilatory acclimatization to hypoxia is absent in highland deer mice, which have a fixed HVR that is effective for gas exchange, through a mechanism that appears independent of evolved changes in the plasticity of CO 2 chemosensitivity. Support or Funding Information Supported by NSERC of Canada.