AUTHOR=Zaitseva Violetta , Arakawa Nanami , Co Carmon , Gomez-Camus Aranza , Perez-Venegas Diego , Montalva Felipe , Gutiérrez Josefina , Ulloa-Contreras Claudia , Chihuailaf Ricardo , Verdugo Claudio , Bienzle Dorothee , Seguel Mauricio TITLE=Systemic inflammation impairs recovery from hookworm-associated anemia in a wild marine mammal host JOURNAL=Frontiers in Immunology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2025.1659969 DOI=10.3389/fimmu.2025.1659969 ISSN=1664-3224 ABSTRACT=Inflammation is a critical defense against pathogens but can impair iron metabolism and erythropoiesis, potentially causing or exacerbating anemia during infection. However, the ecological and evolutionary relevance of this trade-off remains poorly understood. Naturally co-evolved host–parasite systems offer a unique opportunity to explore how inflammatory responses balance the benefits of pathogen control against potential physiological costs. We examined how systemic inflammation affects recovery from hookworm-associated anemia in South American fur seal (Arctocephalus australis) pups, aiming to determine whether inflammation facilitates recovery or imposes hematological constraints. We longitudinally monitored 83 pups over approximately 3 months on Guafo Island, Northern Chilean Patagonia, measuring hookworm burden, hematological parameters, iron concentration, and blood cytokines. Seventy-two percent of the pups developed clinical hookworm infection, and 47% of these became anemic. Among anemic pups, 54% recovered from anemia 2 months after infection. Changes in inflammatory markers, but not hookworm burden, iron concentration, or body condition, predicted recovery outcome. Sustained increases in IFN-γ and neutrophils reduced the likelihood of recovery, while increased IL-10 concentration favored recovery. These effects were independent of plasma iron concentration, although IL-6 was negatively correlated with lower plasma iron. Our findings show that prolonged systemic inflammation impairs recovery from anemia in a wild marine mammal, highlighting a physiological cost of inflammation in early life as a key ecological trade-off between immune defense and hematological resilience in natural host–parasite systems.