Context- and scale-dependent effects of thymol bioactivity on biological networks: contributions from quail under heat stress

A defining feature of healthy function is adaptability, the capacity to dynamically respond to novel and/or unpredictable factors, such as exposition to environmental challenges. Here we explore the role of context (i.e., order in which factors are applied) on the configuration of networks of behavioral and physiological traits from Japanese quail that were supplemented dietary thymol prior, jointly or after onset of a chronic heat stress protocol (i.e., supplementation strategies). Basal diet and standard environmental temperature were used as controls. We begin by showing that each supplementation strategy evolved differently over the 5-week experimental period in regard to body weight and feed-intake. At the end of this experimental period, context-dependency was also observed in the non-trivial functional relationships among 27 traits belonging to 4 subsystems from different spatio-temporal scales. When considered separately, whole-organism level subsystems (i.e. somatic maintenance and egg production traits), are predominantly functionally related to environmental temperature. Conversely, at the molecular level, the liver's antioxidant system response is fundamentally dominated by the supplementation strategy. Interestingly, the serum's antioxidant system shows an intermediate response, not dominated by a given factor. Overall, network configurations were highly dependent on context, and could be associated with specific induced physiological states. Our work constitutes the first study that includes network, integrative, and experimentally comparative analyses applied to the field of dietary supplementation under environmental challenges. This perspective could help understand complex biological responses important for developing efficient and welfare orientated supplementation protocols for farm animals and for interpreting the background in this field. ### Competing Interest Statement The authors have declared no competing interest.