The act of breathing is a complex physiological process involving the interaction of numerous respiratory muscles and a neural control network. These respiratory muscles are the only skeletal muscles in the body whose functioning is necessary to sustain human life, making their ability to resist fatigue very important. Despite this, research has shown that high intensity exercise can induce respiratory muscle fatigue. Given the life-sustaining role of the respiratory muscles, it is important to understand the mechanisms of fatigue, how it is best detected, and how the human body responds and adapts to fatigue. Also, research suggests that physiological and anatomical differences may make women more susceptible to respiratory muscle fatigue compared to men. However, there are no studies that have systematically examined sex-based differences in respiratory muscle fatigue, and the “normal” pulmonary response to exercise in women is not well understood. Jordan Guenette was previously funded by MSFHR for his early PhD work identifying the respiratory limitations women face as they age. Now, he is examining the mechanisms and consequences of respiratory muscle fatigue in men and women during whole body exercise. His study will determine if the smaller lungs and airways in women cause greater respiratory muscle fatigue compared to men. He will also investigate whether high levels of respiratory muscle work reduce blood flow to other parts of the body and are responsible for impairment of whole body exercise performance. Guenette’s project will address questions significant to both basic and clinical science, outlining how men and women differ with respect to the normal pulmonary physiology of exercise. His findings have the potential to influence exercise rehabilitation programs for a variety of patient populations, and exercise prescription to prevent disease in healthy individuals.