This article presents the next stage of research aimed at identifying the impact of input parameters, defined as changes in the design parameters of a marine diesel engine, on selected output parameters treated as diagnostic indicators derived from the rapidly varying exhaust gas temperature signal. In relation to earlier analyses of the individual and simultaneous impact of design parameters and engine load, the novelty of this study lies in assessing and quantifying the effects of interaction between these input factors using the interaction coefficient of significance. Three variable design parameters were analysed: active section area of the intake air duct Ain, injector opening pressure pinj, and compression ratio ε. Based on the rapidly varying exhaust gas temperature, three diagnostic indicators were defined for a single operating cycle of a four-stroke engine: hav, ΔTav and (ΔT/Δτ↑)av. The statistical analysis revealed that the strongest coupled interaction occurs between engine load P and intake air duct area Ain for the average specific enthalpy hav, reaching a positive interaction coefficient of ΔFi = +39.40. In contrast, dynamic indicators (ΔTav and (ΔT/Δτ↑)av) exhibited additive behavior for intake area changes (ΔFi = -1.124), but demonstrated significant positive interactions with injector pressure pinj (ΔFi = +4.12 for ΔTav) and compression ratio ε (ΔFi = +2.28 for both dynamic metrics). The results enabled formulation of conclusions and a criterion for selecting an appropriate diagnostic indicator depending on the analysed functional system of the diesel engine.