Background: Developing students' ability to transfer physiological principles across contexts remains challenging in physiology education. Comparative framing (CF), in which physiological principles are presented through nonhuman examples, may facilitate transfer by organizing reasoning around variation in environmental challenges and physiological function. However, whether benefits arises from CF itself or engagement with physiologically rich examples remains unclear. Methods: A between-semester controlled design was conducted across undergraduate (n = 99) and graduate (n = 43) exercise physiology courses. Semesters were randomly assigned to CF or human-centered framing (HF), with instructional content and structure held constant. Primary outcomes were parallel, non-identical transfer assessments administered before instruction, immediately afterward, and at delayed follow-up. Secondary outcomes included a content equivalence assessment, a two-tier conceptual reasoning measure, and mental effort ratings. Reflective writing was analyzed using inductive thematic analysis. Results: Both conditions demonstrated comparable content acquisition. Significant Framing x Time interactions were observed for Systems and Adaptive Integration and Translational Application, but not Mechanistic Reasoning. The benefits of CF were concentrated in reasoning tasks requiring context-dependent interpretation and integration of physiological principles and became more pronounced at delayed follow-up. Reflective writing analyses converged with the quantitative findings, with the largest thematic differences observed in adaptive versus pathological reasoning. Conclusion: CF produced more durable physiological reasoning despite comparable content learning, suggesting that its educational value extends beyond engaging students with physiologically rich examples alone. Organizing physiology around context, function, and physiological trade-offs may provide a framework for promoting transfer and context-dependent physiological reasoning.