The body masses of extant mammals span over seven orders of magnitude. Within that size range there is extraordinary diversity of function, phylogenetic diversity that understandably presents fertile ground for uncovering biological insights. Remarkably transcending that diversity, are patterns that reveal body size-dependent constraints of "form and function", patterns that become visible only through comparison. Thus, "Comparative Physiology" provides an additional tool for discovery of additional biological insights that may be otherwise hidden. Among these are the linear (isometric) scaling of volumes and the disproportionate (allometric) scaling of biological times and rates. When the diffusion of oxygen through the lungs and tissues is re-examined through this lens it is apparent that body size alone has profound impacts. The smallest mammals have no apparent "structural reserve;" oxygen diffusion in both the lungs and tissues is apparently functioning at full capacity. Because small body size is the ancestral state, it may be an evolutionary consequence of increased body size that large mammals seem to have "excess capacity" for oxygen diffusion in both the lungs and tissues. There is scant evolutionary evidence that physiological variables pivot around "normal" values of humans. Copyright © 2020. Published by Elsevier Inc.