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In this paper, we present Harmony, a holistic messaging middleware for distributed, event-driven systems. Harmony supports various communication paradigms and heterogeneous networks. The key novelty of Harmony is the unified provision of end-to-end quality of service, security, and resiliency, which shields the applications from the underlying network dynamics, failures, and security configurations. We describe the Harmony architecture in the context of cyber-physical business applications and elaborate on the design of its critical system components, including routing, security, and mobility support.