FigShare_Data HbO2 JoP 50 (KMG).xlsx

High-altitude hypoxia constrains tissue O₂ supply, but several high-altitude populations have evolved adaptations to overcome this challenge. Evolved increases in haemoglobin-O₂ (Hb-O₂) affinity are pervasive across high-altitude taxa, but the influence of such increases on aerobic capacity in hypoxia remains contentious. The influence of Hb-O₂ affinity could depend on the capacity to extract O₂ from the blood, but this possibility is poorly understood. We examined this issue in deer mice (<i>Peromyscus maniculatus</i>), which are found from sea level to &gt;4300m elevation in the Rocky Mountains. Mice from populations native to high- and low-altitude were born and raised in captivity. Low-altitude mice were acclimated to warm (25°C) normoxia and high-altitude mice were acclimated to cold (5°C) hypoxia (~12 kPa O₂), creating two groups with distinct capacities for O₂ transport in hypoxia. Aerobic capacity for thermogenesis was measured in hypoxia after each of three pharmacological treatments: saline (control), efaproxiral (decreases Hb-O₂ affinity), and sodium cyanate (increases Hb-O₂ affinity). High-altitude mice generally had greater aerobic capacity in hypoxia, in association with higher arterial O₂ saturation and lower P₅₀ (O₂ pressure at 50% Hb saturation) in most conditions. The P₅₀ at which aerobic capacity was greatest was lower in high-altitude mice than in low-altitude mice. High-altitude mice also had greater uncoupling protein 1 (UCP-1) content in brown adipose tissue and greater cytochrome oxidase activity in gastrocnemius muscle. These results suggest that optimal Hb-O₂ affinity is greater in high-altitude deer mice, in association with a greater capacity to extract and consume O₂ in thermogenic tissues.