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High-altitude life poses physiological challenges to all animals due to decreased environmental oxygen (O₂) availability (hypoxia) and cold. Supporting high metabolic rates and body temperatures with limited O₂is challenging. Many birds, however, thrive at high altitudes. The O₂-transport cascade describes the pathway involved in moving O₂from the environment to the tissues encompassing: (i) ventilation, (ii) pulmonary O₂diffusion, (iii) circulation, (iv) tissue O₂diffusion, and (v) mitochondrial O₂use for ATP production. Shared avian traits such as rigid lungs with cross-current gas exchange and unidirectional airflow aid in O₂acquisition and transport in all birds. Many high-altitude birds, however, have evolved enhancements to some or all steps in the cascade. In this review, we summarize the current literature on gas exchange and O₂transport in high-altitude birds, providing an overview of the O₂-transport cascade that principally draws on the literature from high-altitude waterfowl, the most well-studied group of high-altitude birds. We close by discussing two important avenues for future research: distinguishing between the influences of plasticity and evolution and investigating whether the morphological and physiological differences discussed contribute to enhanced locomotor or thermogenic performance, a potential critical link to fitness. This article is part of the theme issue ‘The biology of the avian respiratory system’. 

The ability to respond rapidly to changes in oxygen tension is critical for many forms of life. Challenges to oxygen homeostasis, specifically in the contexts of evolutionary biology and biomedicine, provide important insights into mechanisms of hypoxia adaptation and tolerance. Here we synthesize findings across varying time domains of hypoxia in terms of oxygen delivery, ranging from early animal to modern human evolution and examine the potential impacts of environmental and clinical challenges through emerging multi-omics approaches. We discuss how diverse animal species have adapted to hypoxic environments, how humans vary in their responses to hypoxia (i.e., in the context of high-altitude exposure, cardiopulmonary disease, and sleep apnea), and how findings from each of these fields inform the other and lead to promising new directions in basic and clinical hypoxia research.