High-volume or exhaustive exercise transiently suppresses immune function and increases infection risk through sustained mitochondrial stress that overwhelms quality control mechanisms, resulting in persistent mtDAMP release and maladaptive inflammation.

When the body performs very intense or long-lasting exercise, its energy-producing mitochondria become overworked and damaged. These damaged mitochondria leak out their internal components, such as DNA and succinate, into the surrounding cells. These leaked components trigger immune sensors that activate inflammatory pathways, causing immune cells to produce excessive signals that keep inflammation going. At the same time, the body's ability to clean up and replace damaged mitochondria is overwhelmed, so the leaks continue. This prolonged inflammation suppresses normal immune defenses, making the body more vulnerable to infections.