Evolution and developmental plasticity of lung structure in high-altitude deer mice

Hypoxia at high altitudes can constrain the ability of endotherms to maintain sufficient rates of pulmonary O2 transport to support exercise and thermogenesis. Hypoxia can also impede lung development during early post-natal life in some mammals, and could thus accentuate constraints on O2 transport at high altitude. We examined how these challenges are overcome in deer mice (Peromyscus maniculatus) native to high altitude. Lung structure was examined in highland and lowland populations of deer mice and lowland populations of white-footed mice (P. leucopus; a congener restricted to low altitude) that were bred in captivity. Among mice that were born and raised to adulthood in normoxia, highland deer mice had higher alveolar surface density and more densely packed alveoli. The increased alveolar surface density in highlanders became fully apparent at juvenile life stages at post-natal day 30 (P30), after the early developmental period of intense alveolus formation before P21. Alveolar surface density was maintained in highlanders that were conceived, born, and raised in hypoxia (~ 12 kPa O2), suggesting that lung development was not impaired by post-natal hypoxia as it is in many other lowland mammals. However, developmental hypoxia increased lung volume and thus augmented total alveolar surface area from P14. Overall, our findings suggest that evolutionary adaptation and developmental plasticity lead to changes in lung morphology that should improve pulmonary O2 uptake in deer mice native to high altitude.